Level of Undernutrition and Its Determinants Among Children Aged 12-59 Months in Wolaita District, Ethiopia.
Undernutrition remains one of the most common causes of morbidity and mortality among children throughout the world particularly in developing countries. The present study aimed to assess the magnitude and associated factors of undernutrition among children aged 12-59 months. A community-based cross-sectional study was conducted in Wolaita district from May to June 2015. Multi-stage stratified systematic random sampling procedure was used. Data were collected using a pretested interviewer-administered questionnaire from 626 children aged 12-59 months. Height and weight were measured by trained data collectors and WHO Anthro version 3.2.2 software was used. Data were entered into Epi Info version 3.3.5 and were exported and analyzed using SPSS version 21. Multivariable logistic regression model with a step-wise method was used to determine the predictors of undernutrition. One third (34.1%; 95% CI 30.4-37.9%) of children were stunted while 6.9% and 11.9% of them were wasted and underweight, respectively, based on WHO Z score <-2. Children live in mother-headed households which often use unprotected sources of water and children who did not get minimum dietary diversity were more likely to be stunted compared to their counterparts. Children residing in rural residences, being a male child, having less power for mother decision-making, presence of diarrhea in the last 2 weeks of the survey and who did not get the minimum dietary diversity were found to be significant determinants of underweight. Children living rural, male sex, their order of birth being 5th and above and who had not got the minimum meal frequency were more likely to be wasted than their counterparts. Undernutrition has a high prevalence in under-5-year-old children of Wolaita district. Under nutrition was associated with female-headed households, unprotected sources of water, below the minimum dietary diversity, rural residence, participation of mother in decision-making, presence of diarrhea, and minimum meal frequency. Thus, nutritional intervention programs in Wolaita district in Ethiopia should focus on these factors.


Reflection holographic filters for compacting optical processors.
Character recognition experiments, carried out with reflection matched filters, are described. The reflection filters are obtained by means of volume holograms, recorded in photographic emulsion and suitably processed. These filters allow a good discrimination among similar characters and exhibit large positioning tolerances. They turn out to be well comparable with transmission hologram filters. An advantage of reflection filters is that the filtering operation can be performed with one-lens processor, thus reducing by one-half the size and the cost of the processor.


Rehabilitation following brain damage: some neurophysiological mechanisms. Animal models of recovery with training after central nervous system lesions.
Animal studies revealed that training with techniques of instrumental conditioning produces another phase of functional recovery beyond spontaneous recovery after CNS lesions. Such conditioned behaviour is difficult to transfer to an unconditioned or another conditioned response. Conditioned and unconditioned behaviours are mediated through different pathways and mechanisms. Conditioned behaviour requires less specific pathways and can probably be achieved as long as the basic spinal mechanisms are activated. Other studies showed that reflex recovery can be maximized through non-specific training, probably by protecting the neuromuscular system from deterioration. However, such a programme does not appear to improve the reflexes beyond the level attributable to spontaneous recovery, nor to facilitate the rate of recovery. If the training is specifically directed towards augmentation of a particular reflex, the reflex can be improved beyond that seen with spontaneous recovery but may be exaggerated to a functional disadvantage. These findings have significant clinical implications.


Timing of calcium and protein synthesis requirements for the first mitotic cell cycle in fertilised Xenopus eggs.
Mitosis is governed by the activity of the M-phase promoting factor (MPF). In some systems, particularly early embryos, transient increases in calcium concentration have been shown to be necessary for mitosis and regulate its timing. By microinjection of the calcium buffer, dibromoBAPTA, into fertilised Xenopus eggs, we have assessed whether calcium events are required to initiate MPF activation and inactivation. Since initial experiments showed that this buffer inhibited protein synthesis, we measured when mitosis and cleavage became independent of translation. We found that, after a period of protein synthesis essential for cleavage, there was a phase during which continued translation affected the timing of cleavage, but was not essential for its occurrence. Measurement of MPF activity in single embryos injected with calcium buffer at different times in the first cell cycle, showed that there were two sensitive periods. The first period of sensitivity blocked MPF activation and coincided with the time at which cleavage became completely independent of protein synthesis. The second sensitive period occurred just before histone kinase activity peaked, and was necessary for kinase inactivation. Preventing inactivation in this way arrested egg extracts in mitosis. These results support the view that transient increases in free calcium concentration contribute to mitotic progression by first triggering MPF activation and subsequently, with elevated MPF activity, inducing its inactivation.


Dkk1 stabilizes Wnt co-receptor LRP6: implication for Wnt ligand-induced LRP6 down-regulation.
The low density lipoprotein receptor-related protein-6 (LRP6) is an essential co-receptor for canonical Wnt signaling. Dickkopf 1 (Dkk1), a major secreted Wnt signaling antagonist, binds to LRP6 with high affinity and prevents the Frizzled-Wnt-LRP6 complex formation in response to Wnts. Previous studies have demonstrated that Dkk1 promotes LRP6 internalization and degradation when it forms a ternary complex with the cell surface receptor Kremen. In the present study, we found that transfected Dkk1 induces LRP6 accumulation while inhibiting Wnt/LRP6 signaling. Treatment with Dkk1-conditioned medium or recombinant Dkk1 protein stabilized LRP6 with a prolonged half-life and induces LRP6 accumulation both at the cell surface and in endosomes. We also demonstrated that Kremen2 co-expression abrogated the effect of Dkk1 on LRP6 accumulation, indicating that the effect of Kremen2 is dominant over Dkk1 regulation of LRP6. Furthermore, we found that Wnt3A treatment induces LRP6 down-regulation, an effect paralleled with a Wnt/LRP6 signaling decay, and that Dkk1 treatment blocked Wnt3A-induced LRP6 down-regulation. Finally, we found that LRP6 turnover was blocked by an inhibitor of caveolae-mediated endocytosis. Our results reveal a novel role for Dkk1 in preventing Wnt ligand-induced LRP6 down-regulation and contribute significantly to our understanding of Dkk1 function in Wnt/LRP6 signaling.


Development and incorporation of hybrid simulation OSCE into in-training examinations to assess multiple CanMEDS competencies in urologic trainees.
As residency training requirements increasingly emphasize a competency-based approach, novel tools to directly evaluate Canadian Medical Education Directives for Specialists (CanMEDS) competencies must be developed. Incorporating simulation allows residents to demonstrate knowledge and skills in a safe, standardized environment. We describe a novel hybrid simulation station for use in a urology resident in-training Objective Structured Clinical Exam (OSCE) to assess multiple CanMEDS competencies. An OSCE station was developed to assess Communicator, Health Advocate, Manager, and Medical Expert (including technical skills) CanMEDS roles. Residents interviewed a standardized patient, interacted with a nurse, performed flexible cystoscopy and attempted stent removal using a novel bladder/stent model. Communication was assessed using the Calgary-Cambridge Observational Guide, knowledge was assessed using a checklist, and technical skills were assessed using a previously validated global rating scale. Video debriefing allowed residents to review their performance. Face and discriminative validity were assessed, and feasibility was determined through qualitative post-examination interviews and cost analysis. All 9 residents (postgraduate years [PGY] 3, 4, 5) completed the OSCE in 15 minutes. Communicator and knowledge scores were similar among all PGYs. Scores in technical skills were higher in PGY-5 compared with PGY-3/4 reside nts (mean score 79% vs. 73%). Residents and exam personnel felt the OSCE station allowed for realistic demonstration of competencies. Equipment cost was $218 for the exam station. We developed and implemented a hybrid simulation-based OSCE station to assess multiple CanMEDS roles. This approach was feasible and cost-effective; it also provided a framework for future development of similar OSCE stations to assess resident competencies across multiple domains.


Pregnancy-specific glycoproteins bind integrin αIIbβ3 and inhibit the platelet-fibrinogen interaction.
Pregnancy-specific glycoproteins (PSGs) are immunoglobulin superfamily members encoded by multigene families in rodents and primates. In human pregnancy, PSGs are secreted by the syncytiotrophoblast, a fetal tissue, and reach a concentration of up to 400 ug/ml in the maternal bloodstream at term. Human and mouse PSGs induce release of anti-inflammatory cytokines such as IL-10 and TGFβ1 from monocytes, macrophages, and other cell types, suggesting an immunoregulatory function. RGD tri-peptide motifs in the majority of human PSGs suggest that they may function like snake venom disintegrins, which bind integrins and inhibit interactions with ligands. We noted that human PSG1 has a KGD, rather than an RGD motif. The presence of a KGD in barbourin, a platelet integrin αIIbβ3 antagonist found in snake venom, suggested that PSG1 may be a selective αIIbβ3 ligand. Here we show that human PSG1 binds αIIbβ3 and inhibits the platelet - fibrinogen interaction. Unexpectedly, however, the KGD is not critical as multiple PSG1 domains independently bind and inhibit αIIbβ3 function. Human PSG9 and mouse Psg23 are also inhibitory suggesting conservation of this function across primate and rodent PSG families. Our results suggest that in species with haemochorial placentation, in which maternal blood is in direct contact with fetal trophoblast, the high expression level of PSGs reflects a requirement to antagonise abundant (3 mg/ml) fibrinogen in the maternal circulation, which may be necessary to prevent platelet aggregation and thrombosis in the prothrombotic maternal environment of pregnancy.


α- and β-Naphthoflavone synergistically attenuate H2O2-induced neuron SH-SY5Y cell damage.
Previous studies have demonstrated an association between neurological diseases and oxidative stress (OS). Naphthoflavone is a synthetic derivative of naturally occurring flavonoids that serves an important role in the treatment and prevention of OS-related diseases. The current study was designed to apply α- and β-Naphthoflavone individually and in combination to counteract the detrimental effects of OS on neurons in vitro. Neuronal SH-SY5Y cells were subjected to 20 µM H2O2, followed by exposure to 20 µM α-Naphthoflavone and/or 10 µM β-Naphthoflavone. Results indicated that α- and β-Naphthoflavone effectively antagonized the apoptosis-promoting effect of H2O2 on neuronal SH-SY5Y cells, and that β-Naphthoflavone significantly (P<0.05) reversed H2O2-inhibited cell viability. Notably, co-treatment of α- and β-Naphthoflavone reversed the H2O2-induced apoptosis rate elevation and cell viability reduction. Further analysis demonstrated that H2O2 inhibited the activities of antioxidant enzymes including catalase, superoxide dismutase and glutathione peroxidase, but this was reversed by the co-treatment with α- and β-Naphthoflavone and selectively enhanced by the treatment with α- or β-Naphthoflavone. H2O2-stimulated p38 mitogen-activated protein kinase activation was repressed following treatment with α- and/or β-Naphthoflavone, along with a decreased expression of the apoptosis-related factors and inhibited caspase-3 activation. In conclusion, co-treatment with α- and β-Naphthoflavone minimized H2O2-led neuron damage compared with treatment with α- or β-Naphthoflavone, suggesting a synergetic effect between α- and β-Naphthoflavone. This indicates that utilizing α- and β-Naphthoflavone together in the clinical setting may provide a novel therapeutic for neurological disease.


Intraoperative single-dose radiotherapy. Observations on staging and interstitial treatment of unresectable liver metastases.
Fourteen patients with a history of colonic cancer were evaluated for metastatic disease and were thought to have unresectable disease confined to the liver. Exploratory surgery revealed that two patients had extensive extrahepatic disease, and the procedure was terminated. In 12 patients, closed-end needles (diameter, 2.1 mm) were introduced into each nodule and connected to a 370-MBq (10-Ci) afterloading iridium source. Radiation doses were dependent on nodule size, providing minimum doses of 20 Gy (2000 rad) to the lesion's periphery with rapid radiation falloff avoiding toxic effects to adjacent normal tissue. The maximum number of nodules treated in one patient was 11. The largest nodule treated measured 9 x 6.5 x 6 cm. Cholecystectomy in four patients allowed precise implantation and obviated biliary fistula. Preoperative computed tomography underestimated the number of hepatic metastases in all cases but one, and treatment-induced computed tomographic alterations further limited its utility. Radiation treatment was well tolerated, and the median hospitalization was eight days. Of ten patients whose preoperative carcinoembryonic antigen values exceeded 10 ng/dL, the values in six patients decreased postoperatively.


BIRADS features-oriented semi-supervised deep learning for breast ultrasound computer-aided diagnosis.
We propose a novel BIRADS-SSDL network that integrates clinically-approved breast lesion characteristics (BIRADS features) into task-oriented semi-supervised deep learning (SSDL) for accurate diagnosis of ultrasound (US) images with a small training dataset. Breast US images are converted to BIRADS-oriented feature maps (BFMs) using a distance-transformation coupled with a Gaussian filter. Then, the converted BFMs are used as the input of an SSDL network, which performs unsupervised stacked convolutional auto-encoder (SCAE) image reconstruction guided by lesion classification. This integrated multi-task learning allows SCAE to extract image features with the constraints from the lesion classification task, while the lesion classification is achieved by utilizing the SCAE encoder features with a convolutional network. We trained the BIRADS-SSDL network with an alternative learning strategy by balancing the reconstruction error and classification label prediction error. To demonstrate the effectiveness of our approach, we evaluated it using two breast US image datasets. We compared the performance of the BIRADS-SSDL network with conventional SCAE and SSDL methods that use the original images as inputs, as well as with an SCAE that use BFMs as inputs. The experimental results on two breast US datasets show that BIRADS-SSDL ranked the best among the four networks, with a classification accuracy of around 94.23 ± 3.33% and 84.38 ± 3.11% on two datasets. In the case of experiments across two datasets collected from two different institutions/and US devices, the developed BIRADS-SSDL is generalizable across the different US devices and institutions without overfitting to a single dataset and achieved satisfactory results. Furthermore, we investigate the performance of the proposed method by varying the model training strategies, lesion boundary accuracy, and Gaussian filter parameters. The experimental results showed that a pre-training strategy can help to speed up model convergence during training but with no improvement of the classification accuracy on the testing dataset. The classification accuracy decreases as the segmentation accuracy decreases. The proposed BIRADS-SSDL achieves the best results among the compared methods in each case and has the capacity to deal with multiple different datasets under one model. Compared with state-of-the-art methods, BIRADS-SSDL could be promising for effective breast US computer-aided diagnosis using small datasets.


[Effect of proteolytic enzymes on the functional activity of the neuron].
Different neuronal responses to electrical stimuli under the effect of proteolytic enzymes, were shown. Different mechanisms of neuronal responses to stimuli were shown to depend on disturbances in neuroglial interrelationships. Two forms of the firing rate transformation depending on the type of stimulation, were described.


Data mining framework for fatty liver disease classification in ultrasound: a hybrid feature extraction paradigm.
Fatty liver disease (FLD) is an increasing prevalent disease that can be reversed if detected early. Ultrasound is the safest and ubiquitous method for identifying FLD. Since expert sonographers are required to accurately interpret the liver ultrasound images, lack of the same will result in interobserver variability. For more objective interpretation, high accuracy, and quick second opinions, computer aided diagnostic (CAD) techniques may be exploited. The purpose of this work is to develop one such CAD technique for accurate classification of normal livers and abnormal livers affected by FLD. In this paper, the authors present a CAD technique (called Symtosis) that uses a novel combination of significant features based on the texture, wavelet transform, and higher order spectra of the liver ultrasound images in various supervised learning-based classifiers in order to determine parameters that classify normal and FLD-affected abnormal livers. On evaluating the proposed technique on a database of 58 abnormal and 42 normal liver ultrasound images, the authors were able to achieve a high classification accuracy of 93.3% using the decision tree classifier. This high accuracy added to the completely automated classification procedure makes the authors' proposed technique highly suitable for clinical deployment and usage.


Elevated mutation rates in the germ line of first- and second-generation offspring of irradiated male mice.
Mutation rates at two expanded simple tandem repeat loci were studied in the germ line of first- and second-generation offspring of inbred male CBA/H, C57BL/6, and BALB/c mice exposed to either high linear energy transfer fission neutrons or low linear energy transfer x-rays. Paternal CBA/H exposure to either x-rays or fission neutrons resulted in increased mutation rates in the germ line of two subsequent generations. Comparable transgenerational effects were observed also in neutron-irradiated C57BL/6 and x-irradiated BALB/c mice. The levels of spontaneous mutation rates and radiation-induced transgenerational instability varied between strains (BALB/c>CBA/H>C57BL/6). Pre- and postmeiotic paternal exposure resulted in similar increases in mutation rate in the germ line of both generations of CBA/H mice, which together with our previous results suggests that radiation-induced expanded simple tandem repeat instability is manifested in diploid cells after fertilization. The remarkable finding that radiation-induced germ-line instability persists for at least two generations raises important issues of risk evaluation in humans.


The dinoflagellate Alexandrium minutum affects development of the oyster Crassostrea gigas, through parental or direct exposure.
Harmful algal blooms are a threat to aquatic organisms and coastal ecosystems. Among harmful species, the widespread distributed genus Alexandrium is of global importance. This genus is well-known for the synthesis of paralytic shellfish toxins which are toxic for humans through the consumption of contaminated shellfish. While the effects of Alexandrium species upon the physiology of bivalves are now well documented, consequences on reproduction remain poorly studied. In France, Alexandrium minutum blooms have been recurrent for the last decades, generally appearing during the reproduction season of most bivalves including the oyster Crassostrea gigas. These blooms could not only affect gametogenesis but also spawning, larval development or juvenile recruitment. This study assesses the effect of toxic A. minutum blooms on C. gigas reproduction. Adult oysters were experimentally exposed to A. minutum, at environmentally realistic concentrations (102 to 103 cells mL-1) for two months during their gametogenesis and a control group, not exposed to A. minutum was fed with a non-toxic dinoflagellate. To determine both consequences to next generation and direct effects of A. minutum exposure on larvae, the embryo-larval development of subsequent offspring was conducted with and without A. minutum exposure at 102 cells mL-1. Effects at each stage of the reproduction were investigated on ecophysiological parameters, cellular responses, and offspring development. Broodstock exposed to A. minutum produced spermatozoa with decreased motility and larvae of smaller size which showed higher mortalities during settlement. Embryo-larval exposure to A. minutum significantly reduced growth and settlement of larvae compared to non-exposed offspring. This detrimental consequence on larval growth was stronger in larvae derived from control parents compared to offspring from exposed parents. This study provides evidence that A. minutum blooms, whether they occur during gametogenesis, spawning or larval development, can either affect gamete quality and/or larval development of C. gigas, thus potentially impacting oyster recruitment.


Constriction of the femoral vein following inguinal hernia repair.
The present paper describes constriction of the femoral vein following hernioplasty ad modum McVay. In five cases, constriction of the femoral vein was demonstrated by phelbography, and pulmonary embolism by pulmonary scintigraphy. It is suggested that a number of postoperative thromboembolisms following hernia repair are caused by a unobserved constriction of the femoral vein. Moreover, constriction of the femoral vein following hernia repair occurs in a number of cases without thromboembolism.


Evaluation of the Compliance of Orthodontists to Infection Control Procedures in Turkey.
Orthodontists do not perform surgical procedures, nevertheless they are obliged to practice appropriate sterilization techniques to prevent cross-infection. This is also important from an ethical and legal point of view. The aim of the present study is to evaluate the compliance of orthodontists to infection control procedures in Turkey. A questionnaire with 36 items was delivered by e-mail to a total of 1152 orthodontists/residents between October 2014 and March 2015 by the Turkish Orthodontic Society. Various data from surveys were analyzed using the IBM SPSS statistics 22 software. The questionnaire was completed by 130 (11.28%) respondents. 95.4% of the orthodontists were immunized against hepatitis B. The usage rates of type B autoclave, non-type B autoclave, and dry-heat sterilizer were 40%, 17.7%, and 16.9%, respectively. A total of 24.6% of the orthodontists used disinfectant solutions for the sterilization of hand instruments and pliers; the rate of using disinfectants for the sterilization of dental handpieces was found to be higher (56.9%). The infection control procedures in the field of orthodontics must be improved in Turkey. Training on compliance with the infection control principles should be included in education programs, and these programs should be repeated on a regular basis.


Comparative toxicity evaluation of targeted anticancer therapeutics in embryonic zebrafish and sea urchin models.
Cancer drug resistance and poor selectivity towards cancer cells demand the constant search for new therapeutics. PI3K-Akt-mTOR and RAS-MAPK-ERK signaling pathways are key mechanisms involved in cell survival, proliferation, differentiation, and metabolism and their deregulation in cancer can promote development of therapy resistance. We investigated the effects of targeted inhibitors (wortmannin, GSK690693, AZD2014 and tipifarnib) towards these two pathways on early zebrafish and sea urchin development to assess their toxicity in normal, fast proliferating cells. PI3K inhibitor wortmannin and RAS inhibitor tipifarnib displayed highest toxicity while GSK690693, a pan-Akt kinase inhibitor, exhibited a less significant impact on embryo survival and development. Moreover, inhibition of the upstream part of the PI3K-Akt-mTOR pathway (wortmannin/GSK690693 co-treatment) produced a synergistic effect and impacted zebrafish embryo survival and development at much lower concentrations. Dual mTORC1/mTORC2 inhibitor AZD2014 showed no considerable effects on embryonic cells of zebrafish in concentrations substantially toxic in cancer cells. AZD2014 also caused the least prominent effects on sea urchin embryo development compared to other inhibitors. Significant toxicity of AZD2014 in human cancer cells, its capacity to sensitize resistant cancers, lower antiproliferative activity against human normal cell lines and fast proliferating embryonic cells could make this agent a promising candidate for anticancer therapy.


Autologous blood use in obstetrics.
The use of autologous blood is of growing concern in the practice of obstetrics. Although prior donation of one's blood for later surgical use and the emergency use of reinfused blood have become established practices, obstetrical use remains controversial because only small groups of women have been studied. This paper gives a brief overview of current issues and use of autologous blood donation in pregnancy and in intraoperative obstetrical procedures.


Relationships between depression, health‑related behaviors, and internet addiction in female junior college students.
Depressive emotions can lead to subsequent unhealthy behaviors such as Internet addiction, especially in female adolescents; therefore, studies that examine the relationships among depression, health‑related behaviors, and Internet addiction in female adolescents are warranted. To examine (1) the relationship between depression and health-related behaviors and (2) the relationship between depression and Internet addiction. A cross-sectional study design was adopted using a structured questionnaire to measure depression, health-related behaviors, and Internet addiction in female adolescents. The data were collected from students of a junior college in southern Taiwan using convenience sampling to select the participants. The questionnaire was divided into four sections: demographics, the Center for Epidemiologic Studies Depression Scale (CES-D), the Health Promoting Lifestyle Profile (HPLP), and the Internet Addiction Test (IAT). The final sample comprised 503 female junior college students, with the participants mainly aged between 15 to 22 years (mean age = 17.30 years, SD = 1.34). Regarding the HPLP scores, the overall score, nutrition subscale score, and self-actualization subscale score were significantly and negatively associated with the CES-D depression score (p < 0.05-0.01). In other words, depression level was lower in students who exhibited more healthy behaviors, put more emphasis on dietary health, and had higher levels of self-admiration and confidence toward life. Regarding the IAT scores, the overall score and six domain scores were all positively associated (p < 0.01) to the CES-D depression score. In other words, the higher an individual's Internet addiction score was, the higher her depression level was. The results confirmed the relationship between depression, health-related behaviors, and Internet addiction. The cultivation of health-related behaviors may help in lowering depressive symptoms. Teenagers with depression have higher risks of developing Internet addiction, and such addiction is likely to affect their daily functioning.


An In-Solution Hybridisation Method for the Isolation of Pathogen DNA from Human DNA-rich Clinical Samples for Analysis by NGS.
Studies on DNA from pathogenic organisms, within clinical samples, are often complicated by the presence of large amounts of host, e.g., human DNA. Isolation of pathogen DNA from these samples would improve the efficiency of next-generation sequencing (NGS) and pathogen identification. Here we describe a solution-based hybridisation method for isolation of pathogen DNA from a mixed population. This straightforward and inexpensive technique uses probes made from whole-genome DNA and off-the-shelf reagents. In this study, Escherichia coli DNA was successfully enriched from a mixture of E.coli and human DNA. After enrichment, genome coverage following NGS was significantly higher and the evenness of coverage and GC content were unaffected. This technique was also applied to samples containing a mixture of human and Plasmodium falciparum DNA. The P.falciparum genome is particularly difficult to sequence due to its high AT content (80.6%) and repetitive nature. Post enrichment, a bias in the recovered DNA was observed, with a poorer representation of the AT-rich non-coding regions. This uneven coverage was also observed in pre-enrichment samples, but to a lesser degree. Despite the coverage bias in enriched samples, SNP (single-nucleotide polymorphism) calling in coding regions was unaffected and the majority of samples had over 90% of their coding region covered at 5× depth. This technique shows significant promise as an effective method to enrich pathogen DNA from samples with heavy human contamination, particularly when applied to GC-neutral genomes.


Infantile overnutrition in the first year of life: a field study in Dudley, Worcestershire.
A survey of feeding patterns and nutrient intake in relation to the growth of 300 normal infants up to 1 year of age in Dudley, Worcestershire, highlights a problem of overnutrition in the group; 50 (16.7%) were found to be suffering from infantile obesity and a further 83 (27.7%) were overweight.During the first three months of life the daily energy intakes of 136 cal/kg body weight for boys and 149 for girls were markedly greater than the level of 120/kg recommended by the Department of Health and Social Security. This coincided with the early addition of solid foods to a full milk intake. 119 babies (39.7%) were offered solids before they were 4 weeks old and 280 (93.3%) before 13 weeks of age. Some babies had solids from the first week after birth. Protein intake was persistently high throughout the first year, and the mean intake of 32.7 g/day was much greater than the intake of 20 g for infants aged up to 1 year recommended by the Department of Health. Standards for fat and carbohydrate intake are not available but in comparison with the levels reported in breast-fed babies intake of fat and carbohydrate was high in the first three months and came closer to the desired level for the former and remained slightly high for the latter in the subsequent age quarters.The relation of childhood and subsequent adult obesity to infant feeding patterns is not yet clear, but there is a high correlation between obese parents and obese and overweight babies; had these babies not been overfed the condition might have been prevented.


Alzheimer's disease in the omics era.
Recent progresses in high-throughput technologies have led to a new scenario in investigating pathologies, named the "Omics era", which integrate the opportunity to collect large amounts of data and information at the molecular and protein levels together with the development of novel computational and statistical tools that are able to analyze and filter such data. Subsequently, advances in genotyping arrays, next generation sequencing, mass spectrometry technology, and bioinformatics allowed for the simultaneous large-scale study of thousands of genes (genomics), epigenetics factors (epigenomics), RNA (transcriptomics), metabolites (metabolomics) and proteins(proteomics), with the possibility of integrating multiple types of omics data ("multi -omics"). All of these technological innovations have modified the approach to the study of complex diseases, such as Alzheimer's Disease (AD), thus representing a promising tool to investigate the relationship between several molecular pathways in AD as well as other pathologies. This review focuses on the current knowledge on the pathology of AD, the recent findings from Omics sciences, and the challenge of the use of Big Data. We then focus on future perspectives for Omics sciences, such as the discovery of novel diagnostic biomarkers or drugs.


Experimental simplification of the excimer laser-assisted nonocclusive anastomosis (ELANA) technique.
The excimer laser-assisted nonocclusive anastomosis (ELANA) technique facilitates the construction of an end-to-side anastomosis between a donor vessel and a recipient artery without the need to temporarily occlude the recipient artery. To test whether the surgically difficult ELANA technique can be simplified. In 42 rabbits, with the aorta as the recipient artery and human saphenous veins as donor grafts, we made 30 conventional ELANAs with 8 microsutures, 90 ELANAs with 4 microsutures (ELANA-4s), 40 ELANAs with 2 microsutures (ELANA-2s), and 90 sutureless ELANAs (SELANAs). SELANA involved a new ring design with 2 pins. ELANA-4, ELANA-2, and SELANA were each combined with 3 different sealants (Bioglue, Tachoseal, and Tisseel) and compared regarding application time, complications, and burst pressure. The conventional ELANA was constructed in a mean of 14.8 +/- 2.6 minutes. All experimental anastomoses were constructed significantly faster; the ELANA-4 in a mean of 10.9 +/- 1.3 minutes, the ELANA-2 in a mean of 5.4 +/- 1.7 minutes, and the SELANA in a mean of 2.5 +/- 1.8 minutes. All ELANA and ELANA-4 anastomoses were sufficiently strong with a burst pressure > 200 mm Hg, except for 1 insufficiently sealed ELANA-4 anastomosis. ELANA-2 was sufficiently strong only with Bioglue, showing a burst pressure > 280 mm Hg. SELANA was sufficiently strong with Bioglue or TachoSil, showing a burst pressure > 260 mm Hg. The ELANA technique can be simplified by reducing or even abandoning microsutures. Of the experimental anastomoses tested, we consider the SELANA technique combined with TachoSil of most potential benefit. Long-term survival studies will be performed in animals before we consider using any of these new techniques in patients.


Time course of low- and high-volume strength training on neuromuscular adaptations and muscle quality in older women.
This study investigated the effects of low- and high-volume strength trainings on neuromuscular adaptations of lower- and upper-body muscles in older women after 6 weeks (6WE), 13 weeks (13WE), and 20 weeks (20WE) of training. Healthy older women were assigned to low-volume (LV) or high-volume (HV) training groups. The LV group performed one set of each exercise, while the HV group performed three sets, 2 days/week. Knee extension and elbow flexion one-repetition maximum (1-RM), maximal isometric strength, maximal muscle activation, and muscle thickness (MT) of the lower- and upper-body muscles, as well as lower-body muscle quality (MQ) obtained by ultrasonography, were evaluated. Knee extension and elbow flexion 1-RM improved at all time points for both groups; however, knee extension 1-RM gains were greater for the HV group after 20WE. Maximal isometric strength of the lower body for both groups increased only at 20WE, while upper-body maximal isometric strength increased after 13WE and 20WE. Maximal activation of the lower and upper body for both groups increased only after 20WE. Both groups showed significant increases in MT of their lower and upper body, with greater gains in lower-body MT for the HV group at 20WE. MQ improved in both groups after 13WE and 20WE, whereas the HV group improved more than the LV group at 20WE. These results showed that low- and high-volume trainings have a similar adaptation time course in the muscular function of upper-body muscles. However, high-volume training appears to be more efficient for lower-body muscles after 20 weeks of training.


The ascendance of laparoscopic splenectomy.
The application of laparoscopic techniques for abdominal procedures has been achieved with varying success. The general acceptance of laparoscopic splenectomy (LS) may be hindered by its infrequent performance and difficulty in manipulating the spleen. A retrospective review of splenectomies performed for primary splenic pathology was done to assess the role and outcome of LS. One hundred fifty LSs were performed from July 1995 through September 1999. Over that time period the proportion of LS performed increased steadily from 17 to 75 per cent of all splenectomies. The primary indications for splenectomy included immune thrombocytopenic purpura in 75 (50%), lymphoma/leukemia 36 (24%), and splenomegaly 19 (13%). There were 86 females and 64 males. Immediately before operation 36 patients (4%) had a platelet count <50,000/ mL, and 24 patients (16%) a hemoglobin <10 mg per cent. The mean operative time was 161 minutes with an average blood loss of 138 cm3 (<50-800). The mean morcellated weight of the entire group was 411 g (33-3300) indicating generally large splenic size. In the 37 patients with splenomegaly the mean weight was 735 g (293-3300). There were two conversions to open splenectomy. Two patients with hematologic malignancy, splenomegaly, and cytopenias died from overwhelming post-splenectomy sepsis (1.3%). Morbidity occurred in 14 (9%) with the most common complication being pancreatitis in seven (5%). The median length of postoperative stay was 2.4 days (range 1-5). In summary LS has rapidly replaced the open approach for nearly all elective splenectomies in adults and children. When performed with the patient in the lateral position it can be accomplished with minimal morbidity, even in complex patients, including those with splenomegaly.


Adaptation, Implementation Plan, and Evaluation of an Online Tobacco Cessation Training Program for Health Care Professionals in Three Spanish-Speaking Latin American Countries: Protocol of the Fruitful Study.
Tobacco cessation training programs to treat tobacco dependence have measureable effects on patients' smoking. Tobacco consumption in low- and middle-income countries (LMICs) is high and slowly decreasing, but these countries usually lack measures to face the epidemic, including tobacco cessation training programs for health professionals and organizations. Based on a previous online smoking cessation training program for hospital workers in Spain, the Fruitful Study aims to increase smoking cessation knowledge, attitudes, self-confidence, and performance interventions among health care professionals of three Spanish-speaking low- and middle-income Latin American and Caribbean (LAC) countries. The purpose of this paper is to describe the methodology and evaluation strategy of the Fruitful Study intended to adapt, implement, and test the effectiveness of an online, evidence-based tobacco cessation training program addressed to health professionals from Bolivia, Guatemala, and Paraguay. This study will use a mixed-methods design with a pre-post evaluation (quantitative approach) and in-depth interviews and focus groups (qualitative approach). The main outcomes will be (1) participants' attitudes, knowledge, and behaviors before and after the training; and (2) the level of implementation of tobacco control policies within the hospitals before and after the training. To date, adaptation of the materials, study enrollment, and training activities have been completed. During the adaptation, the main mismatches were language background and content adaptation. Several aids were developed to enable students' training enrollment, including access to computers, support from technicians, and reminders to correctly complete the course. Follow-up data collection is in progress. We have enrolled 281 hospital workers. Results are expected at the beginning of 2017 and will be reported in two follow-up papers: one about the formative evaluation and the other about the summative evaluation. There is a need to learn more about the cultural and content elements that should be modified when an online tobacco cessation training program is adapted to new contexts. Special attention should be given to the personal and material resources that could make the implementation possible. Results from the Fruitful Study may offer a new approach to adapting programs to LMICs in order to offer education solutions with the use of emerging and growing communication technologies. Clinicaltrials.gov NCT02718872; https://clinicaltrials.gov/ct2/show/NCT02718872 (Archived by WebCite at http://www.webcitation.org/6mjihsgE2).


[The effect of laser puncture on the functional indices of the mammalian body].
Biologically active points (acupuncture points) and reflexogenic zones of Wistar rats of different age were exposed to He-Ne laser radiation with the subsequent control of acetylcholine esterase activity, electric parameters of skeletal muscles and heart, and physical activity. Laser puncture was shown to increase the sympathetic nervous system tonus which was manifested by the decreased acetylcholine esterase activity and increased heart rate. Laser puncture stimulated the growth of membrane potential and increased considerably the performance capability of animals, particularly of three-month-olds.


Inter-related in vitro effects of androgens, fatty acids and oxidative stress in prostate cancer: a mechanistic model supporting prevention strategies.
Oxidation of mitochondrial fatty acids (FA) results in the generation of reactive oxygen species (ROS) which have been postulated to play a key role in the initiation and progression of prostate cancer (PC). We previously reported that androgens increase FA uptake into PC cells. We thus examined if androgens that are known to induce ROS generation regulate FA oxidation in PC cells. The effects of the androgen-depleted medium, R1881 (synthetic androgen) and/or androgen receptor blocker, bicalutamide were examined in the human androgen-responsive but not dependent 22rv1 cells. R1881 supplementation significantly increased mitochondrial FA oxidation ((14)C-radiolabeled FA degradation studies), resulting in increased ROS production. Androgens increased the mRNA levels of carnitine palmitoyltransferase (CPT1), the rate limiting enzyme in the process of mitochondrial FA oxidation. Treatment with R1881 and bicalutamide inhibited these androgen regulated effects. Inhibition of mitochondrial ROS generation by two different inhibitors, rotenone and thenoyltrifluoroacetone, eliminated the androgen-induced ROS generation, to the same level as in cells deprived of androgens or treated with R1881 and bicalutamide. Taken together, androgens increase the mitochondrial oxidation of FA, leading to increased production of ROS that is associated with prostate cell proliferation and mutagenesis. These results therefore support the rationale for PC prevention using 5-alpha reductase inhibitors, dietary restrictions or anti-oxidants, each of which has different inhibitory but complementary effects.


Serum C-reactive protein and CRP genotype in pediatric inflammatory bowel disease: influence on phenotype, natural history, and response to therapy.
C-reactive protein (CRP) is an acute phase reactant. Patients with pediatric inflammatory bowel disease (PIBD) differ from adult patients with inflammatory bowel disease with regard to phenotype, inflammatory profile, and treatment response. We hypothesized that variations in CRP and CRP genotype influence PIBD phenotype, natural history, and remission after anti-tumor necrosis factor alpha therapy. Six single nucleotide polymorphisms tagging CRP (rs1935193, rs1130864, rs1205, rs1417938, rs11265263, and rs1800947) were genotyped in 465 patients with PIBD (diagnosed <17 yr). Phenotyping was serially performed until last follow-up and serum CRP levels recorded at diagnosis and before biological therapy in a subgroup. CRP haplotype (ATGCTC) differed in those diagnosed <10 years, with rs1205T more frequent in Crohn's disease (CD) than ulcerative colitis (UC) (P = 0.009); the haplotype ATGCTC was less frequent in UC (P = 0.002). Three single nucleotide polymorphisms (rs1205, rs1130864, and rs1417938) showed association with elevated CRP levels at diagnosis. CRP genotype had no association with CD phenotype or natural history. CRP was more frequently raised at diagnosis in CD than UC (63% versus 22%, P < 0.0001). Elevated CRP at diagnosis was associated with a higher risk of progression to surgery in patients with CD (P < 0.0001) and the need for azathioprine in the overall PIBD cohort (P = 0.002). There was no effect of CRP genotype or serum CRP on the achievement of remission using anti-tumor necrosis factor alpha therapy. CRP and CRP genotype differ between pediatric patients with CD and UC with a high inflammatory burden at diagnosis suggesting a worse prognosis. Additional evaluation of CRP in inflammatory bowel disease pathogenesis and natural history is now warranted.


The experience of breastfeeding the late preterm infant: a qualitative study.
Breastfeeding confers several health advantages to both infants and mothers. For reasons that are multifactorial, infants born even a few weeks prematurely are less likely to initiate breastfeeding, and those who breastfeed do so for a shorter duration than term infants. Qualitative analysis of structured telephone interviews was used to examine the breastfeeding experience of mothers of late preterm infants. Our study found that, among mothers of late preterm infants, breastfeeding is both a positive bonding experience and a challenging experience, fraught with physical and medical struggles and feelings of guilt and failure. When looking back at the breastfeeding experience, many mothers recount negative experiences of milk supply concerns and breast pumping and report aspiring to be able to feed at breast more and pump less with their next child. Mothers of late preterm infants reported that breastfeeding was a bonding experience for themselves and their infants, and many plan to do it again if they have future children. However, these mothers also reported that their breastfeeding experience included challenges with latching and milk supply, inadequate lactation support from providers after hospital discharge, and feelings of failure. Interventions with the potential to improve the breastfeeding experience of mothers of late preterm infants include (1) nipple shields and other devices to assist with latching, (2) hand expression or supplementation with small volumes of donor milk or formula to help limit the burden of pumping, (3) provider education to improve lactation support after hospital discharge, and (4) peer support groups.


Tumor-associated MICA is shed by ADAM proteases.
The immunoreceptor NKG2D promotes immunosurveillance of malignant cells and protects the host from tumor initiation by activating natural killer cells and costimulating CD8 T cells. NKG2D-mediated recognition of malignant cells by cytotoxic lymphocytes is enabled through the tumor-associated expression of NKG2D ligands (NKG2DL) resulting from cellular or genotoxic stress. Shedding of NKG2DL is thought to constitute a major countermechanism of tumor cells to subvert NKG2D-mediated immunosurveillance. Here, we report that the prototypical NKG2DL MICA is released by proteolytic cleavage in the stalk of the MICA ectodomain, where deletions, but not alanine substitutions, impede MICA shedding. Small compound-mediated stimulation and inhibition of MICA shedding adduced characteristics that indicated an involvement of members of the "a disintegrin and metalloproteinase" (ADAM) family. Accordingly, MICA shedding by tumor cells was inhibited by silencing of the related ADAM10 and ADAM17 proteases, which are known to promote tumor growth by releasing epidermal growth factor receptor ligands. Collectively, our data show that ADAM10 and ADAM17 are critically involved in the tumor-associated proteolytic release of soluble MICA facilitating tumor immune escape. Hence, therapeutic blockade of ADAM10 and ADAM17 seems promising for cancer treatment by targeting both growth and immune escape of tumors.


Detecting insect pollinator declines on regional and global scales.
Recently there has been considerable concern about declines in bee communities in agricultural and natural habitats. The value of pollination to agriculture, provided primarily by bees, is >$200 billion/year worldwide, and in natural ecosystems it is thought to be even greater. However, no monitoring program exists to accurately detect declines in abundance of insect pollinators; thus, it is difficult to quantify the status of bee communities or estimate the extent of declines. We used data from 11 multiyear studies of bee communities to devise a program to monitor pollinators at regional, national, or international scales. In these studies, 7 different methods for sampling bees were used and bees were sampled on 3 different continents. We estimated that a monitoring program with 200-250 sampling locations each sampled twice over 5 years would provide sufficient power to detect small (2-5%) annual declines in the number of species and in total abundance and would cost U.S.$2,000,000. To detect declines as small as 1% annually over the same period would require >300 sampling locations. Given the role of pollinators in food security and ecosystem function, we recommend establishment of integrated regional and international monitoring programs to detect changes in pollinator communities.


Exploring the validity of assessment in anatomy: do images influence cognitive processes used in answering extended matching questions?
Assessment is an important aspect of medical education because it tests students' competence and motivates them to study. Various assessment methods, with and without images, are used in the study of anatomy. In this study, we investigated the use of extended matching questions (EMQs). To gain insight into the influence of images on the validity of test items, we focused on students' cognitive processes while they answered questions with and without images. Seventeen first-year medical students answered EMQs about gross anatomy, combined with either labeled images or answer lists, while thinking aloud. The participants' verbal reports were transcribed verbatim and then coded. Initial codes were based on a task analysis and were adapted into final codes during the coding process. Results showed that students used more cues from EMQs with images and visualized more often in EMQs with answer lists. Ready knowledge and verbal reasoning were used equally often in both conditions. In conclusion, EMQs with and without images elicit different results in this think aloud experiment, indicating different cognitive processes. They seem to measure different skills, making them valid for different testing purposes. The take-home message for anatomy teachers is that questions without images seem to test the quality of students' mental images while questions with images test their ability to interpret visual information. It makes sense to use both response formats in tests. Using images from clinical practice instead of anatomical drawings will help to improve test validity.


[Methodological study of different qualities of filter paper in the radioimmunological determination of thyrotropin in newborn infants].
In the screening of newborns for congenital hypothyroidism, filter paper cards act as sample carriers for capillary blood specimens, and for reference quantities of the measured hormones. Therefore, the quality of the filter paper is especially important and must be taken into account. Different types of filter paper and different guide marks on the paper surface for spotting blood specimens were investigated. The hormone distribution within the dried blood spot and the time necessary to extract the hormones were examined in relation to the sensitivity and yield of the test kit.


An analysis of score patterns of children with attention disorders on the Sensory Integration and Praxis Tests.
The purpose of this study was to identify and describe the score patterns of children with attention deficit hyperactivity disorder (ADHD) on the Sensory Integration and Praxis Tests (SIPT) and to determine whether their score patterns differ significantly from those of children without ADHD. In this retrospective study, the score patterns of 309 children with ADHD were compared with a group of 309 children without ADHD. The children were matched by norm group (reflecting age), gender, and the presence or absence of a learning disability. Both descriptive statistics and multivariate techniques were used. Subjects with ADHD demonstrated relative strengths in the areas of nonmotor visual perception and localization of tactile input and weaknesses with vestibular processing and in most areas of praxis or motor planning. Certain SIPT scores of subjects with ADHD were found to differ significantly from those of subjects without ADHD. The SIPT test that best discriminated the two groups was Space Visualization. The results suggest that it may be helpful for therapists to consider the areas of praxis and vestibular processing in the evaluation and treatment of children with ADHD and that in clinical practice, it would be difficult to distinguish children with ADHD from those without on the basis of their SIPT scores. However, the ways in which the SIPT score patterns of children with ADHD differed from those without assist our understanding of the brain areas and neurological systems involved in children with ADHD.


Guideline for validation of the LAL test as an end-product endotoxin test for human and biological drug products.
The draft guideline sets forth acceptable conditions for use of the Limulus Amebocyte Lysate (LAL) test. It also describes procedures for using this methodology as an end-product endotoxin test for human (including biological products) and animal injectable drugs, and medical devices. Manufacturers are allowed to switch from the rabbit pyrogen test to the LAL test, without preclearance from FDA, if they follow the guideline.


[Vinorelbin in the treatment of breast cancer: current status and prospectives for the future].
To evaluate efficacy and tolerability of vinorelbine in breast cancer. A review of most significant and recent clinical trials was performed. Vinorelbine as single agent showed 44% and 17.36% of response as 1st and 2nd line treatment, respectively. When combined with other agents, these figures were the following: cisplatin, 73%-75% and 43-64%; mitomycin C, up to 92% and 33%-69%; 5-fluorouracil, 33%-64% and 22%-55%; ifosfamide, 57% and 28%; taxol, 78% and 54%; taxotere, up to 80%; mitoxantrone, 44%-68% and 31%-40%; doxorubicin, 57%-82% and 30%-33%; epirubicin, 22%-78% and 33%. Vinorelbine-epirubicin combination appears to be very active in neoadjuvant setting, with up to 92% response rates. Vinorelbine activity is significant and similar to that of the most active antineoplastic drugs in breast cancer. The most promising combinations appear to be with anthracyclines, taxanes or mitomycin C, even in heavily pretreated patients. Some aspects, such as optimal dose and scheduling and the inclusion in adjuvant programs or in new combination regimens remain to be defined.


Reduced number of alpha- and beta-adrenergic receptors in the myocardium of rats exposed to tobacco smoke.
The concentration of alpha- and beta-adrenergic receptors--as measured by specific [3H]WB-4101 and (-)-[3H]dihydroalprenolol binding--was diminished by 60% below control values in the hearts of rats exposed to tobacco smoke. These changes in receptor numbers took place almost immediately after tobacco smoke exposure and were rapidly reversible after termination of the exposure. The dissociation constant, KD, for [3H]WB-4101 was identical in exposed (KD = 0.34 +/- 0.09 nM) and control (KD = 0.35 +/- 0.07 nM) hearts but was significantly different in the case of (-)-[3H]dihydroalprenolol binding (exposed, KD = 2.83 +/- 0.30 mM vs. control KD = 5.22 +/- 0.61 nM). For beta-receptor binding there was no significant difference between exposed and control animals in the Ki values for (-)-epinephrine, (-)-norepinephrine, (-)-alprenolol, (+/-)-propranolol or timolol. (-)-Isoproterenol, however, was found to bind with lower affinity in exposed compared with control hearts. For alpha-receptor binding there was no significant difference between control and 'smoked' animals in the Ki values for (-)-epinephrine, (-0)-norepinephrine or phentolamine. The decrease in alpha- and beta-adrenergic receptor concentration may be related to the phenomenon of receptor desensitization resulting from a release of catecholamines in rats exposed to tobacco smoke.


Occupation, socioeconomic status, and brain tumor mortality: a death certificate-based case-control study.
The relationships between brain tumor mortality and occupation and socioeconomic status (SES) were evaluated in a death certificate-based case-control study. The cases consisted of 904 white men aged 20 years and older who died of a brain tumor in Washington state between 1969 and 1978. For each case a white male control of the same age was chosen. A consistent pattern of increasing risk with increasing SES was seen for all brain tumors as well as for gliomas and astrocytomas. After adjustment for SES, stationary engineers were found to be at excess risk across all histologies based on six cases vs no controls with lower 95% confidence intervals of 2.3 for all brain tumors, 2.8 for gliomas (based on three cases), and 2.1 for astrocytic tumors (based on two cases). Excesses of astrocytic tumors also were observed for petroleum refinery workers (OR = 8.8, CI = 2.2-35.2), forestry workers (OR = 8.5, CI = 1.1-63.4), and cleaning service workers (OR = 2.7, CI = 1.1-6.7).


Eight and 12 week courses of cyclophosphamide in nephrotic syndrome.
Seventy-three children with steroid dependent minimal change nephrotic syndrome were randomly allocated to receive treatment with cyclophosphamide (2 mg/kg/day) for either eight or 12 weeks, in combination with prednisolone. All patients had previously relapsed while the dosage was being reduced or within 14 days of discontinuing prednisolone in the six months before receiving cyclophosphamide treatment (steroid dependent), and had severe steroid toxicity. Thirty two patients were treated with cyclophosphamide for eight weeks, and 41 for 12 weeks. There were no differences between the two groups in age at onset of nephrosis or entry into the study, sex ratio, duration of nephrosis, number of relapses before entry, and follow up period after entry. The relapse free rate of patients treated for eight weeks (25%) was similar to that of those treated for 12 weeks (24%) five years after stopping the treatment, and the mean relapse free interval and the sparing effect of cyclophosphamide (if any) on subsequent treatment with steroids did not differ between the groups. We conclude that cyclophosphamide should be used for no longer than eight weeks at a dose of 2 mg/kg/day in children with steroid dependent minimal change nephrotic syndrome.


Drastic sex-dependent etiological distribution in severe liver diseases from Gabon.
Chronic liver diseases still represent a worrying public health issue in Sub-Saharan Africa. In this region, emphasis is generally made on hepatocellular carcinoma (HCC) albeit liver cirrhosis (LC) is also responsible for an important death toll. Very few studies have compared the presentation and etiologies of cancer and cirrhosis of the liver in Middle Africa. We conducted a comparative retrospective analysis of 74 and 134 cases of patients with HCC and LC treated in Libreville, Gabon. Viral or lifestyle risk factors, clinical symptoms, and biological features were compared. We observed that ages of diagnosis were 53.2 ± 15.7 years and 48.6 ± 18.6 years for HCC and LC with remarkably low M:F sex ratios (1.3-1.8). Ethanol consumption was highly prevalent in both disease types (65.0%-70.0%). Chronic viral infections with hepatitis B (HBV) or C (HCV) virus were also widespread with slight domination of the former in both diseases (43.4% vs. 34.3%, and 35.9% vs. 28.5%). Patients with HCC were presenting very late with a mean diameter of the main nodule of 84 ± 50 mm and a multifocal pattern in 72.7% of cases. HCC developed on a cirrhotic liver in 91.7% of cases. Serum AFP was frankly elevated (>400 ng/ml) in only 35.8% of HCC cases. The most striking feature of the HCC series was the contrasted contribution of distinct pathogenic etiologies involving sex, viral, metabolic, and toxic factors. A frequently dysmetabolic condition synergizing with hepatitis C (anti-HCV, 73.8% vs 22.7%, p < 0.0001) in females and a male cancer promoted by recreational toxicants and chronic hepatitis B (HBsAg, 83.5% vs 35.9%, p < 0.0001) were observed. Men with HCC were considerably younger than women (46.8 ± 14.5 years vs. 62.2 ± 12.2 years, p < 0.0001). Further studies are now warranted to identify routes of HCV transmission and if they are still fueling reservoirs of future patients. Public policies to prevent alcohol-related harm have also to be urgently implemented in Gabon.


Clinical and dosimetric experience with MammoSite-based brachytherapy under the RTOG 0413 protocol.
MammoSite balloon brachytherapy is a relatively new technique for partial breast irradiation. The present paper focuses on the treatment planning, dosimetry, and quality assurance aspects of that treatment, based on the Radiation Therapy Oncology Group 0413 randomized prospective trial (RTOG 0413) protocol. We investigate the usefulness of evaluating implants for treatment appropriateness according to the full set of RTOG criteria as compared with the manufacturer's guidelines. We describe our methods to improve MammoSite balloon implants that would otherwise not comply with the protocol. The initially acquired computed tomography (CT) images are evaluated for tissue conformance, balloon surface-to-skin distance, and balloon symmetry. If the implant fails to meet the foregoing criteria, corrective action such as delay in the CT scan, balloon manipulation, or fluid volume adjustment is taken, and the patient is re-scanned. If the corrective action appears to be successful, three dimensional treatment planning and dose-volume histogram analysis is performed to evaluate the geometric and dosimetric parameters with regard to the RTOG 0413 protocol. The evaluated parameters include, volume ratio of the lumpectomy cavity to the ipsilateral breast, target volume coverage, tissue-balloon conformance, balloon symmetry, minimal balloon surface-to-skin distance, maximum skin dose, and normal breast tissue dose-volume parameters V150 and V200. Among our implants, 21.7% did not initially meet the RTOG 0413 acceptance criteria. Asymmetry and poor conformance values reduce the target volume coverage, and so an implant with moderate conformance and asymmetry can be within the manufacturer's guidelines, but still not meet the RTOG criteria. Our intervention corrected all but one of the implants that failed to meet the criteria. Manipulating the cavity and adjusting the balloon volume may salvage an implant and meet the strict geometric and dosimetric criteria imposed by the RTOG 0413 protocol.


OTUB1 regulates lung development, adult lung tissue homeostasis, and respiratory control.
OTUB1 is one of the most highly expressed deubiquitinases, counter-regulating the two most abundant ubiquitin chain types. OTUB1 expression is linked to the development and progression of lung cancer and idiopathic pulmonary fibrosis in humans. However, the physiological function of OTUB1 is unknown. Here, we show that constitutive whole-body Otub1 deletion in mice leads to perinatal lethality by asphyxiation. Analysis of (single-cell) RNA sequencing and proteome data demonstrated that OTUB1 is expressed in all lung cell types with a particularly high expression during late-stage lung development (E16.5, E18.5). At E18.5, the lungs of animals with Otub1 deletion presented with increased cell proliferation that decreased saccular air space and prevented inhalation. Flow cytometry-based analysis of E18.5 lung tissue revealed that Otub1 deletion increased proliferation of major lung parenchymal and mesenchymal/other non-hematopoietic cell types. Adult mice with conditional whole-body Otub1 deletion (wbOtub1del/del ) also displayed increased lung cell proliferation in addition to hyperventilation and failure to adapt the respiratory pattern to hypoxia. On the molecular level, Otub1 deletion enhanced mTOR signaling in embryonic and adult lung tissues. Based on these results, we propose that OTUB1 is a negative regulator of mTOR signaling with essential functions for lung cell proliferation, lung development, adult lung tissue homeostasis, and respiratory regulation.


Involvement of the renin-angiotensin system in abdominal and thoracic aortic aneurysms.
Aortic aneurysms are relatively common maladies that may lead to the devastating consequence of aortic rupture. AAAs (abdominal aortic aneurysms) and TAAs (thoracic aortic aneurysms) are two common forms of aneurysmal diseases in humans that appear to have distinct pathologies and mechanisms. Despite this divergence, there are numerous and consistent demonstrations that overactivation of the RAS (renin-angiotensin system) promotes both AAAs and TAAs in animal models. For example, in mice, both AAAs and TAAs are formed during infusion of AngII (angiotensin II), the major bioactive peptide in the RAS. There are many proposed mechanisms by which the RAS initiates and perpetuates aortic aneurysms, including effects of AngII on a diverse array of cell types and mediators. These experimental findings are complemented in humans by genetic association studies and retrospective analyses of clinical data that generally support a role of the RAS in both AAAs and TAAs. Given the lack of a validated pharmacological therapy for any form of aortic aneurysm, there is a pressing need to determine whether the consistent findings on the role of the RAS in animal models are translatable to humans afflicted with these diseases. The present review compiles the recent literature that has shown the RAS as a critical component in the pathogenesis of aortic aneurysms.


Association of Multiple High-Risk Factors on Observed Outcomes in Real-World Patients With Advanced Ovarian Cancer Treated With First-Line Therapy.
To identify risk factors for disease progression or death and assess outcomes by risk categories in real-world patients with advanced ovarian cancer. This retrospective study included adult patients from a nationwide electronic health record-derived deidentified database with stage III/IV ovarian cancer who received first-line therapy and had ≥12 weeks of follow-up after index date (end of first-line therapy). Factors predictive of time to next treatment and overall survival (OS) were assessed. Patients were grouped according to the cumulative number of high-risk factors present (stage IV disease, no debulking surgery or neoadjuvant therapy and interval debulking surgery, visible residual disease after surgery, and breast cancer gene [BRCA] wild-type disease/unknown BRCA status), and time to next treatment and OS were assessed. Region of residence, disease stage, histology, BRCA status, surgery modality, and visible residual disease were significant predictors of time to next treatment; age, Eastern Cooperative Oncology Group performance status, disease stage, BRCA status, surgery modality, visible residual disease, and platelet levels were significant predictors of OS (N = 1,920). Overall, 96.4%, 74.1%, and 40.3% of patients had at least 1, 2, or 3 high-risk factors, respectively; 15.7% of patients had all four high-risk factors. Observed median time to next treatment was 26.4 months (95% CI, 17.1 to 49.2) in patients with no high-risk factors and 4.6 months (95% CI, 4.1 to 5.7) in patients with four high-risk factors. Observed median OS was shorter among patients with more high-risk factors. These results underscore the complexity of risk assessment and demonstrate the importance of assessing a patient's cumulative risk profile rather than the impact of individual high-risk factors. They also highlight the potential for bias in cross-trial comparisons of median progression-free survival because of differences in risk-factor distribution among patient populations.


[Conceptual model of interactive open system and the theory of goal attainment of Imogene King].
This work describes the Conceptual Model of Interactive Open Systems and the Theory of Goal Attainment by Imogene King by reflecting on the care process based on this proposal. It was accomplished as a result of the extensive study of King's theoretical structure and its application with patients. It was possible to observe that the theoretical structure supplies the necessary theoretical and conceptual framework which is necessary for humanized nursing care. Also, it remains updated and included in the current context of health care.


Point-of-care testing.
Is POCT worth integrating into a facility? Despite its promise of speed and convenience, this technology requires careful evaluation of potential benefits, disadvantages, and challenges to the existing system. If the pros outweigh the cons, a step-by-step approach can ease the process of implementing a POCT program.


Effect of spatial coherence on damage occurrence in multimode optical fibers.
We investigate the influence of spatial coherence on damage occurrence in highly multimode optical fibers using ultraviolet (UV) nanosecond pulses, with the aim of delivering high fluence in the UV. In some cases, the optical damage is initiated below the fiber facet damage threshold and takes place along the propagation path; such damage is believed to be caused by local constructive interference, creating "hot spots." In order to reduce the degree of spatial coherence, we used a large-diameter core (1.5 mm) fiber as a mode scrambler. Different lengths of this large core fiber were used to deliver energy to a fiber core with a smaller diameter (0.6 mm), in which the damage occurrence was observed. The experimental results indicate that there is a correlation between the degree of spatial coherence and the occurrence of optical damages, typically observed a few millimeters from the fiber facet. Numerical simulations, based on the beam-propagation method, support the degradation of spatial coherence, due to the excitation of high-order modes. Finally, by degrading the spatial coherence of the beam, we establish a new record by delivering more than 100 mJ via a 1.5 mm core diameter fiber in the UV, corresponding to ∼26 times the critical power for self-focusing. Our work sheds light on the ability to deliver high energies of nanosecond-pulsed UV laser radiation through multimode optical fibers.


Amplification, redundancy, and quantum Chernoff information.
Amplification was regarded, since the early days of quantum theory, as a mysterious ingredient that endows quantum microstates with macroscopic consequences, key to the "collapse of the wave packet," and a way to avoid embarrassing problems exemplified by Schrödinger's cat. Such a bridge between the quantum microworld and the classical world of our experience was postulated ad hoc in the Copenhagen interpretation. Quantum Darwinism views amplification as replication, in many copies, of the information about quantum states. We show that such amplification is a natural consequence of a broad class of models of decoherence, including the photon environment we use to obtain most of our information. This leads to objective reality via the presence of robust and widely accessible records of selected quantum states. The resulting redundancy (the number of copies deposited in the environment) follows from the quantum Chernoff information that quantifies the information transmitted by a typical elementary subsystem of the environment.


Measurement of porcine heart temperatures.
During cardiac surgery local hypothermia of the heart is used to slow down cellular metabolism. It has been shown by computer simulation that heart muscle is not uniformly cooled to the desired temperatures. The aim of our work was to find out a way for measuring the temperatures of the ventricular wall and the septum with +/-0.1 degrees C accuracy. The measurement protocol should be applicable during operations on the human heart, during which disturbing factors should be minimized. We have tested the protocol and the equipment on porcine hearts. Two types of probes were tested, the contact-probe, which can be attached to the heart-wall surface, and the needle-probe, which can be inserted into the heart tissue. Before experiments the probes were calibrated and their heat transfer characteristics determined. We conclude that the probes and the protocol are suitable for studying the effects of cardioplegia, and for checking the results previously obtained by computer simulation.


Transforming growth factor beta and epidermal growth factor alter calcium influx and phosphatidylinositol turnover in rat-1 fibroblasts.
Transforming growth factor type beta (TGF beta) alters the cellular response to epidermal growth factor (EGF) for a variety of processes ranging from early transport activities and gene transcription to mitogenesis. In order to test the hypothesis that altered signal transduction mechanisms may mediate both the transforming effects of TGF beta and the modulation of EGF-stimulated processes by TGF beta, we have examined second messenger levels in response to growth factor treatment. The addition of EGF or prolonged treatment with TGF beta increased the rate of 45Ca influx in serum-deprived, confluent Rat-1 cells, while the addition of EGF to TGF beta-pretreated cells produced an additive increase in Ca2+ influx. The stimulation of Ca2+ influx by TGF beta was only observed at incubation times greater than 1 h and was inhibited by inclusion of actinomycin D, suggesting that a newly transcribed gene product was required for the observed response to TGF beta. Both EGF and TGF beta displayed similar time and concentration dependencies for stimulation of Ca2+ influx and for accumulation of inositol trisphosphate (IP3). The increase in IP3 accumulation in response to either EGF or TGF beta required the presence of extracellular Ca2+, and the observed concentration dependencies were similar for the stimulation of phosphatidylinositol turnover and Ca2+ influx. The EGF- and TGF beta-stimulated increases in Ca2+ influx could be blocked by cobalt, cadmium, and [ethylenebis(oxyethylenenitrilo)] tetraacetic acid, but not by specific Ca2+ channel blockers such as nifedipine or verapamil, suggesting that these growth factors do not act via L-type voltage-sensitive calcium channels. Those calcium blockers which inhibited Ca2+ influx also inhibited inositol phosphate release. These data, taken together, indicate that Ca2+ influx and inositol phosphate release are coupled in Rat-1 cells and suggest that influx of Ca2+ from the extracellular medium is responsible for the changes in IP3 accumulation observed in response to both EGF and TGF beta.


Tropomyosin-containing actin cables direct the Myo2p-dependent polarized delivery of secretory vesicles in budding yeast.
The actin cytoskeleton in budding yeast consists of cortical patches and cables, both of which polarize toward regions of cell growth. Tropomyosin localizes specifically to actin cables and not cortical patches. Upon shifting cells with conditionally defective tropomyosin to restrictive temperatures, actin cables disappear within 1 min and both the unconventional class V myosin Myo2p and the secretory vesicle-associated Rab GTPase Sec4p depolarize rapidly. Bud growth ceases and the mother cell grows isotropically. When returned to permissive temperatures, tropomyosin-containing cables reform within 1 min in polarized arrays. Cable reassembly permits rapid enrichment of Myo2p at the focus of nascent cables as well as the Myo2p- dependent recruitment of Sec4p and the exocyst protein Sec8p, and the initiation of bud emergence. With the loss of actin cables, cortical patches slowly assume an isotropic distribution within the cell and will repolarize only after restoration of cables. Therefore, actin cables respond to polarity cues independently of the overall distribution of cortical patches and are able to directly target the Myo2p-dependent delivery of secretory vesicles and polarization of growth.


Transforming growth factor-β-induced differentiation of airway smooth muscle cells is inhibited by fibroblast growth factor-2.
In asthma, basic fibroblast growth factor (FGF-2) plays an important (patho)physiological role. This study examines the effects of FGF-2 on the transforming growth factor-β (TGF-β)-stimulated differentiation of airway smooth muscle (ASM) cells in vitro. The differentiation of human ASM cells after incubation with TGF-β (100 pM) and/or FGF-2 (300 pM) for 48 hours was assessed by increases in contractile protein expression, actin-cytoskeleton reorganization, enhancements in cell stiffness, and collagen remodeling. FGF-2 inhibited TGF-β-stimulated increases in transgelin (SM22) and calponin gene expression (n = 15, P < 0.01) in an extracellular signal-regulated kinase 1/2 (ERK1/2) signal transduction-dependent manner. The abundance of ordered α-smooth muscle actin (α-SMA) filaments formed in the presence of TGF-β were also reduced by FGF-2, as was the ratio of F-actin to G-actin (n = 8, P < 0.01). Furthermore, FGF-2 attenuated TGF-β-stimulated increases in ASM cell stiffness and the ASM-mediated contraction of lattices, composed of collagen fibrils (n = 5, P < 0.01). However, the TGF-β-stimulated production of IL-6 was not influenced by FGF-2 (n = 4, P > 0.05), suggesting that FGF-2 antagonism is selective for the regulation of ASM cell contractile protein expression, organization, and function. Another mitogen, thrombin (0.3 U ml(-1)), exerted no effect on TGF-β-regulated contractile protein expression (n = 8, P > 0.05), α-SMA organization, or the ratio of F-actin to G-actin (n = 4, P > 0.05), suggesting that the inhibitory effect of FGF-2 is dissociated from its mitogenic actions. The addition of FGF-2, 24 hours after TGF-β treatment, still reduced contractile protein expression, even when the TGF-β-receptor kinase inhibitor, SB431542 (10 μM), was added 1 hour before FGF-2. We conclude that the ASM cell differentiation promoted by TGF-β is antagonized by FGF-2. A better understanding of the mechanism of action for FGF-2 is necessary to develop a strategy for therapeutic exploitation in the treatment of asthma.


Exercise-induced hypoalgesia: A meta-analysis of exercise dosing for the treatment of chronic pain.
Increasing evidence purports exercise as a first-line therapeutic for the treatment of nearly all forms of chronic pain. However, knowledge of efficacious dosing respective to treatment modality and pain condition is virtually absent in the literature. The purpose of this analysis was to calculate the extent to which exercise treatment shows dose-dependent effects similar to what is seen with pharmacological treatments. A recently published comprehensive review of exercise and physical activity for chronic pain in adults was identified in May 2017. This report reviewed different physical activity and exercise interventions and their effectiveness in reducing pain severity and found overall modest effects of exercise in the treatment of pain. We analyzed this existing data set, focusing specifically on the dose of exercise intervention in these studies. We re-analyzed data from 75 studies looking at benefits of time of exercising per week, frequency of exercise per week, duration of intervention (in weeks), and estimated intensity of exercise. Analysis revealed a significant positive correlation with exercise duration and analgesic effect on neck pain. Multiple linear regression modeling of these data predicted that increasing the frequency of exercise sessions per week is most likely to have a positive effect on chronic pain patients. Modest effects were observed with one significant correlation between duration and pain effect for neck pain. Overall, these results provide insufficient evidence to conclude the presence of a strong dose effect of exercise in pain, but our modeling data provide tes predictions that can be used to design future studies to explicitly test the question of dose in specific patient populations.


Coconut genome assembly enables evolutionary analysis of palms and highlights signaling pathways involved in salt tolerance.
Coconut (Cocos nucifera) is the emblematic palm of tropical coastal areas all around the globe. It provides vital resources to millions of farmers. In an effort to better understand its evolutionary history and to develop genomic tools for its improvement, a sequence draft was recently released. Here, we present a dense linkage map (8402 SNPs) aiming to assemble the large genome of coconut (2.42 Gbp, 2n = 32) into 16 pseudomolecules. As a result, 47% of the sequences (representing 77% of the genes) were assigned to 16 linkage groups and ordered. We observed segregation distortion in chromosome Cn15, which is a signature of strong selection among pollen grains, favouring the maternal allele. Comparing our results with the genome of the oil palm Elaeis guineensis allowed us to identify major events in the evolutionary history of palms. We find that coconut underwent a massive transposable element invasion in the last million years, which could be related to the fluctuations of sea level during the glaciations at Pleistocene that would have triggered a population bottleneck. Finally, to better understand the facultative halophyte trait of coconut, we conducted an RNA-seq experiment on leaves to identify key players of signaling pathways involved in salt stress response. Altogether, our findings represent a valuable resource for the coconut breeding community.


Effect of collection matrix, platelet depletion, and storage conditions on plasma extracellular vesicles and extracellular vesicle-associated miRNAs measurements.
The interest around circulating extracellular vesicles and their cargo in diagnostics has greatly increased; however, several pre-analytical variables affect their determination. In this study, we investigated the effects of sample matrix, processing, and plasma storage delay and temperature on extracellular vesicles and their miRNA content. Blood was collected from 10 male volunteers in dipotassium ethylendiaminotetraacetate-coated tubes (K2EDTA), either with plasma-preparation tube (PPT) or without (K2E) gel separator. A stepwise centrifugation was applied to K2E aliquots to obtain platelet-poor plasma (PPP). K2E, PPP and PPT plasma, stored under different conditions, were assayed for extracellular vesicles concentration and size distribution, through dynamic laser light scattering, and microRNAs content, by qPCR. PPP samples were characterized by the lowest extracellular vesicles count and miRNA detectability. Although having no effects on extracellular vesicles total concentration, storage conditions influenced microRNAs detectability, mainly in PPP and PPT samples. Extracellular vesicles-associated miRNAs levels in K2E were, in general, higher than in PPP and to a very limited extent to PPT. Storage temperature and delay did not affect their profile in K2E samples. Extracellular vesicles count and extracellular vesicles miRNA profile changed under the analyzed pre-analytical variables, showing the greatest stability in K2E samples. Since pre-analytical variables differently affected extracellular vesicles and their miRNA content, they should be considered in each experimental setting and clinical routine.


Pathological characteristic of Alzheimer's disease produced by lesion in nucleus basalis of Meynert in rats.
To find out if the lesion in nucleus basalis of Meynert (nbM) can induce some morphological changes characteristic of Alzheimer's disease. Kainic acid was injected into nbM of the rats, and the behavioral deficiency and the morphological changes in the cortex and hippocampus were observed by methenamine silver staining and electron microscopical examination. After 9-15 months of breeding following nbM-lesion, we observed many pathological changes in this animal model, which were characteristic of Alzheimer's disease in human, and especially we could find for the first time the formation of senile plagues after 15-month breeding. It is proposed that the degeneration of nbM neurons might be primary and responsible for the pathological changes in other brain tissues in sporadic Alzheimer's disease.


Keratin 8 Is an Inflammation-Induced and Prognosis-Related Marker for Pancreatic Adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) is one of the highest-grade malignancies in the world. More effective biomarkers and treatment plans are necessary to improve the diagnosis rate and clinical outcome. The oncogenesis of PDAC is influenced by several factors, including chronic pancreatitis (CP). Keratin 8 (KRT8) is an important member of the keratin protein family and plays a role in regulating the cellular response to stress stimuli and mediating inflammatory reactions. However, the role of KRT8 in pancreatitis and PDAC is still poorly understood. Here we assessed the differentially expressed genes (DEGs) by bioinformatic methods with expression profiles available online for a caerulein-induced mouse model and human PDAC tissue. The prognostic value was evaluated by Kaplan-Meier analysis and Cox regression analysis. The diagnostic value was evaluated by Receiver Operating Characteristic analysis (ROC). The function of the genes was predicted by protein-protein interaction analysis, correlation analysis, and GO analysis. The conclusion was further validated in rat pancreatitis model, human tissue, and PDAC cell lines, including immunohistochemical staining (IHC), CCK-8 assay, wound healing assay, and flow cytometry. KRT8 was found to be upregulated in murine pancreatitis tissue, human CP tissue, and human PDAC tissue. High expression of KRT8 had a negative impact on the prognosis of PDAC patients. KRT8 was predicted to be involved in the regulation of the migration and viability of PDAC cells, which was validated in PDAC cell lines. Knockdown of KRT8 impaired the migration and proliferation and induced apoptosis in PDAC cell lines. In conclusion, keratin 8 is an inflammation-induced molecule and could serve as a diagnostic and prognostic marker for PDAC patients. More studies are needed for further validation from the perspective of precision and individualized medicine.


In utero gene therapy rescues microcephaly caused by Pqbp1-hypofunction in neural stem progenitor cells.
Human mutations in PQBP1, a molecule involved in transcription and splicing, result in a reduced but architecturally normal brain. Examination of a conditional Pqbp1-knockout (cKO) mouse with microcephaly failed to reveal either abnormal centrosomes or mitotic spindles, increased neurogenesis from the neural stem progenitor cell (NSPC) pool or increased cell death in vivo. Instead, we observed an increase in the length of the cell cycle, particularly for the M phase in NSPCs. Corresponding to the developmental expression of Pqbp1, the stem cell pool in vivo was decreased at E10 and remained at a low level during neurogenesis (E15) in Pqbp1-cKO mice. The expression profiles of NSPCs derived from the cKO mouse revealed significant changes in gene groups that control the M phase, including anaphase-promoting complex genes, via aberrant transcription and RNA splicing. Exogenous Apc4, a hub protein in the network of affected genes, recovered the cell cycle, proliferation, and cell phenotypes of NSPCs caused by Pqbp1-cKO. These data reveal a mechanism of brain size control based on the simple reduction of the NSPC pool by cell cycle time elongation. Finally, we demonstrated that in utero gene therapy for Pqbp1-cKO mice by intraperitoneal injection of the PQBP1-AAV vector at E10 successfully rescued microcephaly with preserved cortical structures and improved behavioral abnormalities in Pqbp1-cKO mice, opening a new strategy for treating this intractable developmental disorder.


Upper Lip Anatomy, Mechanics of Local Flaps, and Considerations for Reconstruction.
Reconstruction of defects involving the upper lip can be challenging. The purpose of this review was to analyze the anatomy and function of the upper lip and provide an approach for reconstruction of upper lip defects. The primary role of the upper lip is coverage of dentition and animation, whereas the lower lip is critical for oral competence, speech, and eating. The orbicularis oris (OO) and several other muscles contribute to upper lip function. There are various insertion points for animation muscles, including the upper lip dermis, OO, and modiolus. Special attention should be paid to the philtrum, Cupid's bow, and vermilion border during reconstruction. Advantages and disadvantages of the Abbe, Estlander, and Karapandzic flaps are presented. Knowledge of mechanics, indications, and properties of local flaps while considering unique characteristics of upper lip anatomy and function are crucial for optimal aesthetic and functional outcomes.


[Preparation of Zinc Dibenzyl Dithiocarbamate and Its Spectral Analysis].
In the study, zinc methyl mercaptobenzimidazole (MMBZ) was synthesized by one-step method. MMBZ was detecued and characterized by FTIR, UV-Vis, XRD, TG-DSC. Its micro-structure and intrinsic regularity were revealed. Chemical bond types into MMBZ molecule were revealed by FTIR. The final product was determined MMBZ. There absorption peaks were detected by UV-Vis at 219.6,245.5,302.2 nm respectively, due to n→σ(*),π→π(*),π→π(*) electronic transitions, led by S—C, benzene and five element heterocyclic in MMBZ molecule. It could provide experimental basis with enterprise to test MMBZ product quality and speculate its structure. It was shown that MMB was a ligand of MMBZ, and its basic structure of MMB was retained still by XRD spectra. The structure of MMBZ molecule was amorphous. Two kinds of information were detected with TG-DSC as quality change and thermal effect. There were five absorption peaks of 67.5, 155.3, 253.7, 324.8, 391.3 ℃, due to impurity solvent decomposition peak, phase transition peak and decomposition of MMBZ respectively. The scheme of one step preparation of composite environment-friendly rubber antioxidant MMBZ was feasible. The structure of MMBZ could be speculated by results of its detecting. It could provide the basis of experimental data on association MMBZ performance, exploring its anti-aging mechanism and extending the scope of MMBZ application.


Fetal Pose Estimation in Volumetric MRI using a 3D Convolution Neural Network.
The performance and diagnostic utility of magnetic resonance imaging (MRI) in pregnancy is fundamentally constrained by fetal motion. Motion of the fetus, which is unpredictable and rapid on the scale of conventional imaging times, limits the set of viable acquisition techniques to single-shot imaging with severe compromises in signal-to-noise ratio and diagnostic contrast, and frequently results in unacceptable image quality. Surprisingly little is known about the characteristics of fetal motion during MRI and here we propose and demonstrate methods that exploit a growing repository of MRI observations of the gravid abdomen that are acquired at low spatial resolution but relatively high temporal resolution and over long durations (10-30 minutes). We estimate fetal pose per frame in MRI volumes of the pregnant abdomen via deep learning algorithms that detect key fetal landmarks. Evaluation of the proposed method shows that our framework achieves quantitatively an average error of 4.47 mm and 96.4% accuracy (with error less than 10 mm). Fetal pose estimation in MRI time series yields novel means of quantifying fetal movements in health and disease, and enables the learning of kinematic models that may enhance prospective mitigation of fetal motion artifacts during MRI acquisition.


Consequences of recombination on traditional phylogenetic analysis.
We investigate the shape of a phylogenetic tree reconstructed from sequences evolving under the coalescent with recombination. The motivation is that evolutionary inferences are often made from phylogenetic trees reconstructed from population data even though recombination may well occur (mtDNA or viral sequences) or does occur (nuclear sequences). We investigate the size and direction of biases when a single tree is reconstructed ignoring recombination. Standard software (PHYLIP) was used to construct the best phylogenetic tree from sequences simulated under the coalescent with recombination. With recombination present, the length of terminal branches and the total branch length are larger, and the time to the most recent common ancestor smaller, than for a tree reconstructed from sequences evolving with no recombination. The effects are pronounced even for small levels of recombination that may not be immediately detectable in a data set. The phylogenies when recombination is present superficially resemble phylogenies for sequences from an exponentially growing population. However, exponential growth has a different effect on statistics such as Tajima's D. Furthermore, ignoring recombination leads to a large overestimation of the substitution rate heterogeneity and the loss of the molecular clock. These results are discussed in relation to viral and mtDNA data sets.


Cross-linked transfer RNA functions in all steps of the translation process.
A specific photochemical reaction between 4-thiouridine and cytosine cross-links two arms of transfer RNA. This cross-link, introduced into phenylalanine transfer RNA and arginine transfer RNA, limits the conformational freedom of the molecule. Both modified transfer RNA's are capable of functioning in all steps of protein synthesis with this restraint on allowable conformations.


Comprehensive characterization of circular RNAs in ~ 1000 human cancer cell lines.
Human cancer cell lines are fundamental models for cancer research and therapeutic strategy development. However, there is no characterization of circular RNAs (circRNAs) in a large number of cancer cell lines. Here, we apply four circRNA identification algorithms to heuristically characterize the expression landscape of circRNAs across ~ 1000 human cancer cell lines from CCLE polyA-enriched RNA-seq data. By using integrative analysis and experimental approaches, we explore the expression landscape, biogenesis, functional consequences, and drug response of circRNAs across different cancer lineages. We revealed highly lineage-specific expression patterns of circRNAs, suggesting that circRNAs may be powerful diagnostic and/or prognostic markers in cancer treatment. We also identified key genes involved in circRNA biogenesis and confirmed that TGF-β signaling may promote biogenesis of circRNAs. Strikingly, we showed that clinically actionable genes are more likely to generate circRNAs, potentially due to the enrichment of RNA-binding protein (RBP) binding sites. Among these, circMYC can promote cell proliferation. We observed strong association between the expression of circRNAs and the response to drugs, especially those targeting chromatin histone acetylation. Finally, we developed a user-friendly data portal, CircRNAs in cancer cell lines (CircRiC, https://hanlab.uth.edu/cRic ), to benefit the biomedical research community. Our study provides the characterization of circRNAs in cancer cell lines and explored the potential mechanism of circRNA biogenesis as well as its therapeutic implications. We also provide a data portal to facilitate the related biomedical researches.


Impaired Visual Search in Children with Rett Syndrome.
This study aims to investigate selective attention in Rett syndrome, a severely disabling neurodevelopmental disorder caused by mutations in the X-linked MECP2 gene. The sample included 28 females with Rett syndrome (RTT) and 32 age-matched typically developing controls. We used a classic search task, in conjunction with eye-tracking technology. Each trial included the target and several distractors. The distractors varied in number and differed from targets in either a "single feature" (color or shape), creating a pop-out effect, or in a "conjunction of features" (color and shape), requiring serial search. Children searched for the target in arrays containing five or nine objects; trials ended when the target was fixated (or 4000 ms elapsed). Children with Rett syndrome had more difficulty finding the target than typically developing children in both conditions (success rates less than 50% versus 80%) and their success rates were little influenced by display size or age. Even when successful, children with RTT took significantly longer to respond (392 to 574 ms longer), although saccadic latency differences were observed only in the single-feature condition. Both groups showed the expected slowing of saccadic reaction times for larger arrays in the conjunction-feature condition. Search failures in RTT were not related to symptom severity. Our findings provide the first evidence that selective attention, the ability to focus on or select a particular element or object in the environment, is compromised by Rett syndrome. They reinforce the notion that gaze-based tasks hold promise for quantifying the cognitive phenotype of RTT.